19. Acute Leukemia

Question 1

Acute Lymphoblastic Leukemia

Answer 1

• Disease of childhood and adolescence (Rare in adults and have a worse prognosis than children)
• Childhood ALL used to be fatal, but now is successfully treated with about 80% cured
• Two main subgroups of ALL: B-Cell & T-Cell (Seen more in adults than children)
• tumor burden, immunophenotype, genetic abnormalities, and organomegally make a worse prognosis

Question 2

Clinical Features of ALL

Answer 2

• Fever (Neutropenia)
• Fatigue (Anemia)
• Mucosal bleeding (thrombocytopenia)
• Lymphadenopathy
• Splenomegally
• Hepatomegally
• Bone pain

Question 3

Laboratory Features of ALL

Answer 3

• Neutropenia
• Half have leukocytosis and may not have circulating lymphoblasts
• Anemia
• Thrombocytopenia
• Malignant cells infiltrating the bone, meminges, testes and ovaries
• Lymphoblasts in cerebral spinal fluid
• T-cell ALL: mass in the mediastinum
• Genetics:
• • B-Cell ALL: Ph chromosome – t(9;22) BCR-ABL (Precursor- B ALL), Hyperdiploidy, Hypodiploidy.
• • T-Cell ALL: Abnormalities are random and aren’t associated with specific biological features or outcomes
• Immunophenotype: CD markers are used to classify subtypes of ALL, B-specific Ags present at different stages of cell development, T-specific Ags

Question 4

Treatments for ALL

Answer 4

• Varies based on genetic findings: Remission Induction Therapy, Consolidation, CNS Therapy
• Methotrexate
• For adults: Vincristine, Daunorubicin, Prednisone, Monoclonal Abs
• For unresponsive or relapse ALL: Peripheral Blood Stem Cell Transplant

Question 5

Acute Myelogenous Leukemia

Answer 5

• Most common leukemia in patients <1 yo and adults (incidence increases with age).
• French American British classification based upon morphology and cytochemistry
• World Health Organization relies on cytogenetics and molecular characterization
• Adults: more common in males than in females
• Prognosis is related to genetic abnormalities, some conferring a better prognosis than others

Question 6

Clinical Features of AML

Answer 6

• Pallor
• Fatigue
• Fever with infections (Neutropenia)
• Bruising (Thrombocytopenia)
• Bleeding (Thrombocytopenia)
• Bone and joint pain (~25%)
• Splenomegally (~50%)
• Lymphnode enlargement rare
• DIC (Disseminated intravascular coagulation)

Question 7

Laboratory Features of AML

Answer 7

• WBC count: 5-30 x 109/L
• Myeloblasts present 90% of the time
• Anemia
• Thrombocytopenia
• Neutropenia
• CSF (cerebral spinal fluid) can have malignant cells
• Hyperuricemia
• Hyperphosphatemia
• Hypocalcemia
• Hypokalemia
• Blast count: 20% threshold doesn’t apply when certain genetic abnormalities are present
• Genetics:
• • Common gene mutations: NPM1, FLT3, CEBPa, JAK2
• • Common translocations: t(15;17) – in APL

Question 8

Tumor Lysis Syndrome

Answer 8

• From induction therapy, especially if WBC elevated
• Metabolic complication in leukemia and lymphoma with and without the treatment of the malignancy
• Caused by the degradation of products of dying cancer cells causing acute uric acid nephropathy and renal failure

Question 9

FAB - M2

Answer 9

• (t(8;21)(q22;q22);RUNX1/RUNX1T1)
• seen in about 5% of AML patients
• Seen in children and young adults
• Myeloblasts w/ dysplastic granular cytoplasm, Auer rods and some maturation
• Pseudo Pelger-Huet cells and hypo granulation
• Diagnosis based upon genetics rather than blast count
• Prognosis is usually favorable, except for presence of monosomy 7

Question 10

Acute Promyelocytic Leukemia

Answer 10

• t(15;17)(q22;q12);PML-RARA)
• 5-10%
• All ages (mostly young adults)
• Differentiation block
• Detection of t(15;17) is enough for diagnosis
• Cells are hyper granular and contain Auer rods
• Treat with vitamin A
• Poor prognosis if there is a lack of response to treatment with Vitamin A

Question 11

Acute Myelomonocytic Leukemia

Answer 11

• Elevated WBC
• Myeloid and monocytoid cells seen in peripheral blood and bone marrow
• Immunophenotype is positive for myeloid and monocytic antigens
• Nonspecific cytogenetic changes

Question 12

Acute Monoblastic and Monocytic Leukemia

Answer 12

• <5%
• Common in younger individuals
• Based upon maturity
• Cells in the marrow and PB are monocytic
• Positive for Non- Specific - Esterase
• Extramedullary involvement
• Bleeding disorders

Question 13

Acute Erythroid Leukemia - M6

Answer 13

• 2 subtypes based upon the presence of myeloblasts:
• • Acute Erythroleukemia: 50% nucleated cells in BM are normoblasts; >20% are myeloblasts
• • Pure Erythroid Leukemia: >50% are pronormoblasts; >30% are basophilic normoblasts
• Hypodiploidy
• +Periodic Acid Schiff
• RBC precursors have dysplastic features
• nRBCs

Question 14

Other Acute Leukemia categories

Answer 14

Megakaryoblastic

• Myeloid Sarcoma
• Myeloid Proliferations Related to Down Syndrome
• Blastic Plasmacytic Cell - Neoplasm
• AL of Ambiguous Lineage